Drugs: aminoglycosides

Question 1

solubility of aminoglycosides

Answer 1

highly water soluble agents so limited ability to cross lipid bilayer

Question 2

what is gentamicin?

Answer 2

aminoglycoside

• boras spectrum of action

generally uesd to treat grma negative bacteria, gram pos staphylococci and gram positive myoplasma

Question 3

what is Tobramycin

Answer 3

clincially interchangable with gentamicin

• mainly used topically to treat bacteria that are resistant to gentamicin
• more expensive tho

Question 4

what is amikacin

Answer 4

resistant to most aminoglycoside-modifying enzymes

used systemicaly to treat bacteria that are resistant to gentamicin

Question 5

what binds and inhibts 50S subunit of ribosome

Answer 5

acrolides, chloramphenicol, lincosamides, streptogramins, oxazolidinones, and pleuromutilins

Question 6

What binds and inhibits the 30S subunit of the ribosome

Answer 6

Aminoglycosides, spectinomycin, and tetracyclines bind to and inhibit the activity of 16S rRNA in the 30S subunit

Question 7

what are tetracyclins

Answer 7

derived from streptomyces bacteria or produced semi synthetic derivates of tetracycline (oxytetracycline)

• considered to have a braod spectrum of activity but mainly used to treat infections caused by atypical bacteria (neither gram pos or gram neg)

Question 8

MOA tetracyclins

Answer 8

• bind 30S subunit of bacterial ribsomse (same as aminoglycosides) to inhibit proten synthesis
• do this by prevening the binding of aminoacyl-tRNA through allosterically binding to the ribosome
• binding is reversible (unlike aminoglycosides) and voerall effect is bacteriostatic not bacteriocidal

Question 9

what bacteria do tetracyclins treat

Answer 9

• activity against gram pos and gram neg aerobes and anerobes but used to treat atypical like rickettsia, chamydia and mycoplasmab

^drug of choice in thsoe situations

• also have activity against some protozoa and effective but slow acting anti-malarial

Question 10

what antimicrobial drugs target teh #) s ribosomal subunit

Answer 10

• streptomycin and gentamicin (aminoglycosides_

Spectinomycin is a structural relative of the aminoglycosides.

Tetracycline and doxycycline are tetracyclines. Tigecycline is a glycylcycline.

Question 11

doxcyline in acne treatment

Answer 11

has anti MMP and ROS scavening properties but also inhibits phospholipase AS

• used to reat rosacea and acne which are inflammatory skin condiitons

Question 12

what are glycylcylines

Answer 12

new class of antibiotcs that are derived from tetracyclines

• Tigecycline is first made vaialble, its based on modification of minocycline that gives it a 5x greater affinity for ribosomal binding allowing it to overcome ribosomal protection
• has large side chain which may inhibit from permeating the efflux pump
• bactteriostatic and broad spec including gram pos, gram neg and anerobic bacteria that are resistant to other drugs

Question 13

what is TMS

Answer 13

aka co-trimoxazole, combo of sulfonamides (S) and trimethoprim (TM) referred to as potentiated sulfonamide (TM + S)

effect is often bactericidal

*sulfonamides are ineffective when used alone

Question 14

what are sulfonamides

Answer 14

aka sulfa drugs, antimicobial agents that contain a sulfonamide group

• inhibit the metabolic pathway required for folic acid synthesis
• sulfonamides are competitive inhbitors of dihydropteroate synthetase - key enzyme in folate synthesis

*alone sulfonammides are bacteriostatic, and not v effective

Question 15

adverse effects of sulfonamides

Answer 15

May be mild or erious

Fiver and skin problems, esp if drug is aplpied topically

Allergies common to oral preps

Precipitation of drug and metabolites in renal tubules of dehydrates patietns may occur and cause renal damage

Kernicterus: rare, displcaemnt of bilirubin from albumin in infants which then crosses the BB. Regions most commonly affected are basal gnaglia, hippocampus and geniculate bodies which cause various signs of brain damage

Question 16

what is ciprofloxacin

Answer 16

Type of fluoroquinolone

Activity spec is similar to gentamycin

can target many Gram negative aerobes but Staphylococcus are essentially the only Gram positive that it will have activity against

used to treat mycoplasma and chlamydia but ciprofloxacin is ineffective against all anaerobes.

Question 17

what are macrolides

Answer 17

Target the 50S ribosomal subunit

Have large lactone ring attached to one or more deoxy sugars

Activity on some atypical bacteria

Mainly bacteriostatic

One of safest antibacterials

Question 18

pharmacokinetics of macrolides

Answer 18

Metabolized and excreted in bile, but erythromycin shown to inhibit P450 metabolism of other drugs - consider before prescribing other meds

Widely distribute except the CNS, one of few antimicrobials that enters prostate relatively well

Also dsitributes well to lungs and concnetrate in lung (can be 100x higher than in plasma)

Question 19

adverse effects of macrolides

Answer 19

Tissue irritation (severe pain with IM admin and vomiting

Vomiting esp problematic with erythromycin

Question 20

MOA of macrolides

Answer 20

Inhibiiton of proien synthesis by binding reversibly to bacterial ribosmoes 50S subunit

causing dissociation of peptide carrying tRNA from ribosome during translocation

Question 21

what is Erythromycin

Answer 21

Most common macrolide similar spectru to amoxicillin

shown to inhibit P450 metabolism of other drugs - consider before prescribing other meds

Major vomiting side effect bc stimulates motilin receptors in GI tract causing nausea (highly variable between aptients)

Question 22

Azithromycin

Answer 22

Newer macrolide that’s more effectie than erythromycin against gram neg aerobes

Logner half life and can be administered once daily rather than 4 times a day

Commonly used for resp tract infections and one of worlds best selling drugs

Question 23

clarithromycin

Answer 23

Newer macrolie

More effective than erythromycin and azithromycin against gram positive apthogens

Logne rhalf life than erythromycin and therefore needs to be admin twice a day

Common to treat community acquired respiratory tract infections

More acid stable than erythromycin so has fewer GI adverse effects

Question 24

what is telithromycin?

Answer 24

Treatment of certant resistant respiratory pathogens

Resistance that develops following administration of macrolides is mainly due to target modification and efflux pumps

macrolides are predominantly prescribed as antimicrobial agents, they also have anti-inflammatory effects that inhibit neutrophil migration and leukotriene synthesis.

Question 25

what is Chloramphenicol

Answer 25

Also targets 50S subunit

Isolated from Streptomyces venezuelae

bacteriostati active against both aerobic and anaerobic Gram positive and Gram negative organisms.

Penetrates the cornea really well

Available on oral, topical and injectible forms

Currently banned in good producing animals due to documented fatailied

Only use in those with serious infections when less potentially dangerous drugs are ineeffective or contraindicted

Question 26

adverse effects of chloramphenicol

Answer 26

Usually very safe but fatal aplastic anemia can occur in humans

Only in 1/30,000 and due to genetic defect that is simialr to malignan hyperthermia

Effect not dose related or irreversible and may occur weeks ro months after therapy is stopped